title: High-sensitivity C-reactive protein and clopidogrel treatment in patients at high risk of cardiovascular events: a substudy from the CHARISMA trial.
abstract: OBJECTIVE
  This study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are at high risk of atherothrombotic events. The predictive value of hsCRP levels for a treatment benefit of clopidogrel was also explored.
  
  
  METHODS
  The study included 8021 patients with established atherosclerotic disease or multiple cardiovascular risk factors enrolled in the CHARISMA trial. Patients were randomly assigned either to clopidogrel plus aspirin or placebo plus aspirin. HsCRP was measured at study entry and at study termination (median 28&emsp14;months). The predefined primary composite endpoint was myocardial infarction, stroke, or death from cardiovascular causes.
  
  
  RESULTS
  There was a stepwise increase in the event rate of the combined primary endpoint with increasing quartiles of hsCRP at baseline (4.0%, 6.1%, 7.4% and 8.7% for the highest quartile). In both treatment groups the changes in hsCRP levels over time were identical. In patients with low hsCRP levels (<3 mg/l) clopidogrel treatment was associated with a lower event rate compared with placebo (4.0% vs 6.0%, log rank p=0.005). In contrast no treatment effect was observed in patients with high hsCRP levels (8.1% vs 8.0%, ns).
  
  
  CONCLUSIONS
  In this broad population, hsCRP is a powerful predictor of ischaemic events. Compared with placebo, clopidogrel was without effect on inflammatory markers. The reduction in cardiovascular events by antiplatelet treatment with clopidogrel was isolated to patients with low levels of hsCRP.
authors.affiliation: Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany. m.weber@kreiskliniken-dadi.de
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Koon-Hou
authors.initials: KH
authors.lastname: Mak
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Easton
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination / Q000379:methods; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin